PRECISION

Acceptable Range Of PrecisionThe minimum requirements for the analytical variability originate from the acceptance criteria of the specificationHowever, at least for drug products, better precisions can usually be achieved. Of course, due to the additional variance components, acceptance criteria should be defined for each level of precision separately.For the same level of precision, some conclusions can be drawn from the distribution of standard deviations or for repeatability. *

For the same level of precision, some conclusions can be drawn from the distribution of standard deviations, as shown in the following, for repeatability. For the purpose of evaluation, it is important to distinguish between individual repeatabilities and the overall repeatability. The former can vary in a certain range around the true standard deviation (depending on the number of determinations, but for the question of acceptability, the upper limit of the distribution is relevant. The latter is an average (pooled) standard deviation describing the variability within the series, and therefore, due to the increased degrees of freedom gives a better estimate of the true (repeatability) standard deviation.*

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*Definitions ICH Guideline Q2A

Intermediate precision expresses within-laboratories variations: different days, different analysts, different equipment, etc. Reproducibility expresses the precision between laboratories.

INTERMEDIATE PRECISIONIt is determined by comparing the results of a method run within a single laboratory over a number of weeks. A methods intermediate precision may reect discrepancies in results obtained from different operators,from inconsistent working practice (thoroughness) of the same operator,from different instruments,with standards and reagents from different suppliers,with columns from different batches, ora combination of these.The objective of intermediate precision validation is to verify that in the same laboratory the method will provide the same results once the development phase is over.

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REPRODUCIBILITYThe objective is to verify that the method will provide the same results in different laboratories. The reproducibility of an analytical method is determined by analyzing aliquots from homogeneous lots in different laboratories with different analysts, and by using operational and environmental conditions that may differ from, but are still within, the specied parameters of the method (inter laboratory tests). Validation of reproducibility is important if the method is to be used in different laboratories.

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*Summarizes factors that should be the same, or different, for precision, intermediate precision, and reproducibility.

EXAMPLE OF THE JOURNAL*

The several methods of validation that discussed in the journalLinearityPrecisionAccuracy RobustnessRuggedness LOD & LOQ

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Precision*

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To be precise... and accurate!To be precise... and accurate!May 9, 2006*